Biomedical subjects
Publications and source records attributed to S Gupta.
A technique of repairing acid burns of the stomach which are followed by fibrosis and stricture formation, is described. The operation has been done on 3 patients with a maximum follow-up of 4 years. The method has an advantage over conventional gastrojejunostomy of enlarging small gastric remnants especially when an oesophageal bypass is either necessary at the same time or later on. Also normal gastroduodenal continuity is maintained.
In forty-six (9 per cent) of 485 patients who were receiving long-term renal hemodialysis, a carpal tunnel syndrome developed in at least one hand. A total of sixty-four surgical procedures were performed for this problem in forty-one patients. All of the forty-one patients reported symptomatic relief, although three had recurrent symptoms. There was no correlation between the time of onset of the carpal tunnel syndrome and such factors as the patient's age, sex, or race; the cause of renal failure; the site of vascular access for hemodialysis; or a history of parathyroidectomy. There was a correlation, however, between the development of the carpal tunnel syndrome, the side of the longest functional vascular access, and the presence of arterial calcifications. In all eleven patients in whom a radial steal syndrome developed, an ipsilateral carpal-tunnel syndrome also developed. It was concluded that factors other than those involving the site of vascular access must have important etiological roles.
This article describes a 1-hour enzyme immunoassay (ELISA) for identifying lymph nodes in which a single immunoglobulin light chain isotype is abnormally predominant. Eighteen lymph nodes representing a variety of reactive hyperplasias and B-cell neoplasms were analyzed with the ELISA and submitted for B- and T-cell gene rearrangement studies at the CT beta, JH and J kappa (JK) loci. In all 18 specimens, there was agreement in the results of the ELISA, the histologic diagnoses, and the results of gene rearrangement studies. In three of the B-cell lymphomas identified by histologic, ELISA, and DNA studies, surface marker phenotyping by flow cytometry did not indicate the presence of a monoclonal cell population. It is concluded that the ELISA correlates well with DNA gene rearrangement studies and is a rapid, simple, and accurate method for identifying lymph nodes containing monoclonal immunoglobulin. Moreover, it is proposed that the ELISA has certain advantages over other methods for determining light chain clonality in clinical specimens, and it is therefore useful to distinguish between benign lymphoid hyperplasia and monoclonal B-cell neoplasms.
Cyclosporin A abrogates pleiotropic drug resistance in certain experimental tumors. Its impact on drug-sensitive tumors has not been investigated. Our studies show that in drug-sensitive Ehrlich ascites carcinoma and hepatoma 129 cyclosporin A enhances daunorubicin inhibition of DNA synthesis in vitro and prolongs survival of host mice in vivo. Of particular interest is that cyclosporin A converts ineffective daunorubicin regimens into those which result in prolongation of host mice survival. Other agents known to reverse pleiotropic drug resistance are reported to exert their effects by increasing intracellular drug accumulation. In contrast, our studies of drug transport in drug-sensitive Ehrlich ascites carcinoma and hepatoma 129 show that cyclosporin A causes minimal enhancement of [3H]daunorubicin uptake without inhibition of [3H]daunorubicin efflux in both the presence and absence of interrupted active daunorubicin efflux. This suggests that the mechanism of action of daunorubicin enhancement by cyclosporin A in drug-sensitive tumors is not simply the result of increased intracellular daunorubicin accumulation. In vivo dosages of cyclosporin A in the current study are comparable to those which can be used with reasonable safety in humans. We conclude that cyclosporin A may be useful in the potentiation of anthracycline antibiotic therapy directed against drug-sensitive as well as drug-resistant tumors.
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Progabide, a gamma-aminobutyric acid agonist, was given to ten patients with essential tremor in a double-blind, placebo-controlled crossover study. The effect of progabide did not differ from that of placebo. Alterations in gamma-aminobutyric acid neurotransmission do not appear to be involved in the pathogenesis of essential tremor.
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A phase I study of the intracarotid administration of PCNU was conducted in patients with intracerebral tumors recurring after cranial radiation. Seventeen patients were treated including 16 with recurrent gliomas or glioblastomas and 1 with recurrent brain metastases from adenocarcinoma of the lung. An additional patient received a vertebral artery infusion of PCNU for a recurrent glioblastoma. Seven of 17 patients receiving intracarotid PCNU responded for a response rate of 41%. If only evaluable patients with gliomas are considered, the response rate was 44%. Tumor grade at time of initial diagnosis, exposure to prior chemotherapy, and dose of PCNU did not appear to have a major impact on response rate. Zubrod performance status 3 patients had a lower response rate (25%) than did patients with performance status 1 or 2 (response rate 63%). Thrombocytopenia and reversible central nervous system toxicity were dose limiting at a PCNU dose of 110 mg/m2. Two patients had possible permanent central nervous system toxicity. Three patients had permanent ipsilateral visual impairment, including one at the lowest dose used into the carotid artery (60 mg/m2). Orbital pain appeared to be substantially less than that seen with intracarotid BCNU but headaches may have been somewhat more common. The single patient receiving a vertebral artery infusion developed marked headaches and restlessness after receiving 25 mg/m2 of a planned 75 mg/m2 treatment into the vertebral artery and the treatment had to be discontinued. Symptoms were rapidly reversible upon stopping the medication. Our overall impression is that intracarotid PCNU causes less ocular pain but more transient central nervous system toxicity than does intracarotid BCNU.(ABSTRACT TRUNCATED AT 250 WORDS)
It is well established that the activation of T lymphocytes by mitogen/antigen is accompanied by a rise in intracellular free calcium ([Ca2+]i), changes in membrane potential, metabolism of inositol phospholipid, and activation of protein kinase C. These early events of signal transduction culminate in late events of lymphocyte activation, namely, DNA synthesis, lymphokine production, and cellular proliferation. In this study we examined the effect of human immunodeficiency virus (HIV) on changes in membrane potential and [Ca2+]i levels. The membrane potentials were markedly decreased (depolarized) in T cell lines infected with HIV (H9/HTLV IIIb) and did not respond normally to phytohemagglutinin (PHA) or anti-T3 (anti-CD3) monoclonal antibody compared to uninfected H9 cell line. The basal [Ca2+]i levels in H9/HTLV IIIb cells were increased in comparison to those in H9 cells; however, there was very little further increase in [Ca2+]i in H9/HTLV IIIb cells following activation with PHA or anti-T3 monoclonal antibody. This is in contrast to a significant rise in [Ca2+]i in H9 cells following similar stimulation. These data demonstrate abnormalities in the plasma membrane potential and [Ca2+]i levels in chronically infected T cells with HIV. These abnormalities in signal transduction of the T-cell activation pathway could be responsible for T-cell dysfunction in patients with HIV infection.
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An HTLV-III/LAV antibody-positive homosexual man in whom disseminated malignant melanoma developed is described. Immunologic analysis revealed an increase in suppressor/cytotoxic phenotype (Leu-2-positive) T cells, depressed proliferative response to mitogens, decreased proportions of T cells with interleukin-2 receptors but normal production of both interleukin-2 and interleukin-1, cutaneous anergy, elevated levels of serum IgG and IgA, and presence of autoantibodies against smooth muscle and parietal cells of the stomach. This case stresses the need for reporting all types of neoplasms associated with exposure to HTLV-III/LAV so that their true incidence in the population "at risk" for the acquired immune deficiency syndrome can be determined.
The immunologic status of a patient with disseminated cryptococcosis and no underlying predisposing factor was evaluated. The proportions and numbers of T cells, T cell subsets, B cells and proliferative responses to mitogens and soluble antigens, including cryptococcal antigen, were comparable to those in healthy control subjects; however, the patient had moderately severe hypogammaglobulinemia. The patient continues to do well clinically with intravenous gammaglobulin and antifungal therapy. This study suggests that antibodies might also play a role in the defense against cryptococcal antigen.
The in vitro effect of ion channel-blocking agents verapamil (V), 4-aminopyridine (4AP), tetraethylammonium (TEA), and quinine (Q) was examined on the proliferative response of human peripheral blood T lymphocytes in the autologous mixed-lymphocyte reaction (AMLR). All the above channel blockers in a dose-dependent manner inhibited the AMLR. Tetramethylammonium (TMA), an analog of TEA that does not block K+ channel currents, did not inhibit the AMLR. 4AP at 1 mM/ml concentration inhibited the expression of IL-2 receptors, as defined by monoclonal antibody anti-Tac, on T-cell activated in the AMLR. In vitro addition of recombinant interleukin 2(rIL-2) completely corrected the inhibition of the AMLR by channel blockers. Furthermore, the concentrations of ion channel blockers required for blocking 50% response of T cells in the AMLR was much lower than that reported for 50% block of T-cell proliferation in response to phytohemagglutinin or in allogeneic mixed-lymphocyte culture (MLC). These data suggest a role of ion channels in T-cell functions and show that the AMLR provides a more sensitive system, as compared to lectin stimulation or MLC, to examine any immunosuppressive effects of ion channel-blocking agents in disease states where they are used as therapeutic modalities.
The study deals with acute/immediate radiation changes in 2020 sequential vaginal smears in 101 patients of carcinoma of the cervix uteri, 97 were of squamous cell carcinoma and 4 of adenocarcinoma. The smears were collected after 12-14 days, 15-24 days and 25 days to 6 weeks following radiotherapy. The pretreatment vaginal smears were collected and examined for percentage of cancer cells. Subsequent smears were studied for radiation changes in benign and malignant cells, such as cell size, vacuolation of cytoplasm, multinucleation and nuclear changes, etc. A gradual and linear decline in cancer cells was observed until the end of therapy; 41.6% of patients had less than 10% cancer cells within 12-14 days of therapy, 63.4% of patients between 15 and 24 days and 74.6% after 25 days to 6 weeks following radiation. Eighty three percent of the patients attained zero level at the end of therapy.
In the T-T AMLR, suppressor functions are generated, and because in human aging a deficiency of suppressor function has been observed, we examined the T-T AMLR in aging humans. Non-T cells were irradiated and used as stimulators against fresh autologous responder T cells to generate activated T cells (TA). TA cells were irradiated and used as stimulators against fresh autologous responder T cells (T-TA AMLR), CD4+ cells (CD4-TA AMLR), or CD8+ cells (CD8-TA AMLR) in the presence or absence of recombinant interleukin 2 (rIL-2). T cells from young and aging subjects were stimulated with phytohemagglutinin and examined for the expression of IL-2 receptors (IL-2R) and transferrin receptors. A significant decrease in T-TA, CD4-TA, and CD8-TA AMLR was observed in aging humans when compared with simultaneously studied sex-matched young controls. In vitro addition of rIL-2 resulted in an enhanced AMLR in both young and aging subjects; however, the total [3H]thymidine incorporation by T cells and T-cell subsets from aging in the presence of rIL-2 was lower than that of young subjects' T cells and T-cell subsets in the presence of rIL-2. The net increase (over the baseline values) in [3H]thymidine incorporation in T-TA and CD8-TA by rIL-2 was significantly less in the aging group when compared to the young group. In contrast, the rIL-2-induced net increase in [3H]thymidine incorporation in CD4-TA AMLR in both groups was comparable. T cells expressing IL-2R and transferrin receptors were of similar proportions in two groups. These data show a deficiency of the T-T AMLR in aging humans that appears to be, at least in part, due to deficient response to rIL-2. This deficiency of the T-T AMLR might be responsible for deficient suppressor activity, hyperimmunoglobulinemia, and the presence of autoantibodies in aging humans.
Acanthamoeba culbertsoni, the free living pathogenic amoeba responsible for fatal meningoencephalitis, contains an S-adenosylmethionine decarboxylase (EC 4.1.1.50) which is strongly activated by putrescine and to a lesser extent by cadaverine; spermidine, spermine, diaminopropane and 1,6-diaminohexane are inactive. Methylglyoxal bis-(guanylhydrazone) competitively inhibited the enzyme with a Ki value of 123 microM. The enzyme was strongly inhibited by berenil (Ki = 0.5 microM) and to a lesser extent by pentamidine. The putrescine-activated enzyme is inhibited by MgCl2. The apparent molecular weight of 110,000 and its enzymatic properties indicate that the enzyme has characteristics intermediate between the bacterial and eukaryotic S-adenosylmethionine decarboxylases.